DNA replication rapidly and accurately produces a complementary replica of genomic DNA; however, on occasion mutations are made. With age, the accumulated effects of these mutations can lead to cancer. The Bacteriophage T7 DNA replication fork serves as a model for the study of DNA replication. It is both extensively characterized and simple, comprising only 4 proteins. The central protein forming the replication fork is helicase/primase (gp4) which coordinates both leading strand and lagging strand DNA synthesis. For leading strand synthesis, gp4 unwinds double stranded DNA while tightly coupled to the leading strand DNA polymerase. For lagging strand synthesis, gp4 synthesizes tetraribonucleotide primers de novo and transfers the primer to the lagging strand polymerase active site in a transient complex. To understand how gp4 catalyzes these reactions and how it interacts with DNA polymerase, the crystal structures of T7 helicase/primase (gp4) will be pursued by the following three strategies (i) crystallization of gp4 alone or in complex with nucleotides (2) crystallization of gp4 with DNA polymerase in a lagging strand complex containing a DNA template, dideoxy-terminated primer, and ddNTP (3) crystallization of gp4 complexed with DNA polymerase in a leading strand complex. Crystals have been obtained of gp4 hexamer alone. Experimental conditions have been established for the formation of stable gp4-polymerase complexes.